Our studies conducted in the last year on obsessive-compulsive disorder (OCD) have had a primary focus on treatment of the disorder with clomipriame. Investigation conducted here and elsewhere have conclusively shown that this tricyclic drug is more effective than structurally similar tricyclics such as desipramine, imipramine, and amitriptyline. In contrast, in depression, panic disorder, and other psychiatric disorders, these agents have essentially identical efficacy. In a double-blind study attempting to evaluate what duration of clomipramine maintenance treatment might be most useful, we found that patients treated for 5 to 27 months all had a similar, very high relapse rate during placebo substitution for seven weeks. As all patients responded to clomipramine reinstatement, it appears that longer term maintenance treatment with this agent is useful. In studies evaluating possible serotonergic contributions to clomipramine's therapeutic effects, evidence was found brain serotonin subsystems (those mediating some behaviors and temperature) but not others (those mediating cortisol and prolactin responses) were down-regulated during clomipramine treatment of OCD patients.